过敏性哮喘患者支气管肺泡灌洗液外切酶体与细胞因子和白三烯的产生
2012/07/05
摘要
背景:白三烯(LT)是一类非常强的促炎介质,参与哮喘的致病。外切酶体为纳米级的载体,由多种细胞释放后刺激或下调免疫反应,但取决于原始细胞的状态和特性。我们近期研究显示,肺结节病患者的支气管肺泡灌洗液(BALF)中外切酶体发生变化,但外切酶体在哮喘中的作用尚不清楚。本试验旨在研究BALF中的外切酶体是否影响LT的生物合成,探寻哮喘患者BALF外切酶体的表型和功能特征。
方法:收集13名健康个体和对桦树花粉过敏的12名轻度过敏性哮喘患者(桦树花粉过敏原激发前后)的支气管肺泡灌洗液外切酶体。流式细胞仪和western blot检测外切酶体特征。分别采用ELISA和反相HPLC检测人支气管上皮细胞株(16HB14o-)中的外切酶体诱导IL-8和LT产生的能力。
结果:与健康个体相比,哮喘患者BALF中的外切酶体相关标志物(如四旋蛋白CD63和CD81和清除剂受体CD36)较高。过敏原激发前后BALF外切酶体未见显著差异。此外, BALF外切酶体含有LT生物合成所需的酶。哮喘患者外切酶体促进BECLTC(4)和IL-8释放的能力显著增加,CysLT(1)受体拮抗剂(孟鲁司特)能抑制外切酶体诱导的IL-8分泌。
结论:哮喘患者和健康者支气管肺泡灌洗液外切酶体的表现型和功能存在显著差异。哮喘患者BALF外切酶体通过增加气道上皮的细胞因子和LTC(4)而导致亚临床气道炎症。
(林江涛 审校)
Allergy. 2012 May 23. doi: 10.1111/j.1398-9995.2012.02835.x. [Epub ahead of print]
Bronchoalveolar lavage fluid exosomes contribute to cytokine and leukotriene production in allergic asthma.
Torregrosa Paredes P, Esser J, Admyre C, Nord M, Rahman QK, Lukic A, Rådmark O, Grönneberg R, Grunewald J, Eklund A, Scheynius A, Gabrielsson S.
Source
Department of Medicine Solna, Translational Immunology Unit, L2:04, Karolinska Institutet, University Hospital, Stockholm, Sweden.
Abstract
BACKGROUND: Leukotrienes (LTs) are potent pro-inflammatory mediators involved in asthma. Exosomes, nanosized vesicles released from various cells, can stimulate or down-regulate immune responses, depending on the state and nature of the originating cell. We have recently shown an altered exosome profile in bronchoalveolar lavage fluid (BALF) of patients with sarcoidosis, but their role in asthma is unknown. Our aims were to investigate whether exosomes from BALF have LT biosynthetic capacity and to explore phenotypic and functional characteristics of BALF exosomes in asthma.
METHODS: Bronchoalveolar lavage fluid exosomes were collected from healthy individuals (n = 13) and patients with mild allergic asthma to birch pollen (n = 12) before and after birch allergen provocation. Exosomes were characterized by flow cytometry and Western blot. Their capacity to induce IL-8 and LT production in the human bronchial epithelial cell (BEC) line 16HB14o- was measured by ELISA and reverse-phase HPLC, respectively.
RESULTS: Compared to BALF exosomes from healthy individuals, BALF exosomes from asthmatics displayed higher levels of exosome-associated markers, such as the tetraspanins CD63 and CD81 and the scavenger receptor CD36. No major differences were observed between BALF exosomes from before and after allergen provocation. Furthermore, we show that BALF exosomes contain enzymes for LT biosynthesis. The effect of exosomes to promote LTC(4) and IL-8 release in BEC was significantly increased for exosomes from asthmatics, and the CysLT(1) receptor antagonist Montelukast reduced exosome-induced IL-8 secretion.
CONCLUSIONS: Bronchoalveolar lavage fluid exosomes from asthmatic and healthy individuals exhibit distinct phenotypes and functions. BALF exosomes from asthmatics might contribute to subclinical inflammation by increasing cytokine and LTC(4) generation in airway epithelium.
Allergy. 2012 May 23. doi: 10.1111/j.1398-9995.2012.02835.x. [Epub ahead of print]
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过敏原诱导哮喘的鼠模型
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